Absract Archive
October 2007
Feature ReviewPharmacogenetics to Pharmacogenomics
IntroductionPharmacogenetics (PGt) is the field of science in which relation between response to a drug and variations in a particular gene is studied so that a drug can be optimized based on individual needs. The relationship between response to drug and gene variations was realized when a fixed dose of drug given for a particular disease showed different response in different individuals. As summarized in figure 1, apart from the individuals who responded normally to the drug, there were people who did not respond at all or who showed hyperactive response to the dosage. This hyperactivity led to severe adverse side reactions or death in some cases. Drug response has also been shown to be gender specific with females being more sensitive than males [25]. Additionally, an individual can respond to same drug in different ways at different points of time (like development of resistance towards a medication). But this has less significance when compared to former points because variations in drug response are often greater among members of a population than they are within the same person at different times (or between monozygotic twins) [20].
Apart from the hyperactive response induced by the drug, there are cases where a drug acts sub-optimally than desired, thereby necessitating the need of higher doses of drug which may cause undesirable side effects. Thus, the time and money spent in fitting a drug to a patient seem to be wastage of resources, palpable more in financially disabled sectors of society. Therefore, a need to regularize the action of drug or development of drug according to a person's genetic make-up was felt for safe, effective and less expensive medicines. The process of translating pharmacogenetic (PGt) and pharmacogenomics (PGx) research into clinical practice for the benefit of the patient in terms of more efficient treatment with no or low side effects with the reasonable cost is yet to be achieved. These technologies are market driven towards clinical applications to diagnose diseases or predict the efficacy of the drug. The applications of PGx can be optimally utilized in drug discovery and development with the combination of other genomic and proteomic technologies.Authors:Asmita , Praveshika, Meenakshi, V.R.Swamy.
ReviewProtein Based Drugs -A Molecular Tool in Diagnosis
IntroductionThe future of pharmacy belongs to a special category of therapeutics and diagnostics referred to as protein-based drugs. To date, modern medicine has relied heavily on synthetically or chemically produced drugs to treat or prevent diseases and conditions.
However, developments in the field of molecular biology have led to an increase in our knowledge of biological systems and their interactions. For example, scientists know more about the sources of many diseases and how the human body fights diseases. They are now focussing on using the body's own tools to fight diseases by developing therapeutics that mimic the actions of the body's arsenal.
What are Proteins?
Proteins are biomolecules that are essential in determining the structure and carrying out most of the functions in living cells that make up all living organisms. They are made up of individual units called Amino acids, which although similar in structure, have different characteristics. There are about 20 different amino acids in nature and these assemble in chains of varying lengths to form proteins. The order of amino acids determines the structure and function of the protein. This order is specified by genes.
Proteins in living organisms are classified according to their biological roles. These include :
Enzymatic - Proteins that trigger all the chemical reactions that occur in the cells of living organisms.
Transport - Proteins that carry other substances throughout the body or molecules across cell membranes. For instance, the Protein Haemoglobin carries oxygen from the lungs to other parts of the body.
Structural - Proteins that help in supporting functions in the body. For instance, Keratin is the protein that is important for supporting hair and other skin parts.
Storage - Proteins that store amino acids. For instance, casein is the protein in milk that provides a source of amino acids for baby mammals.
Hormonal - Proteins that coordinate bodily activities. For instance, Insulin is the protein hormone secreted by the pancreas that regulates the level of sugar in the blood.
Receptor - Proteins that are built into the membrane of a cell and detect chemical signals released by other cells. They contribute to the cell's response to the chemical stimuli.
Contractile - Proteins that help in movement. For example, Actin and myosin are responsible for the movement of muscles.
Defensive - Protect the body against diseases. For example, Antibodies are proteins that protect the body against viruses and harmful bacteria.
Author:.K.Jeyaprakash,
Research article
Urinary Marker Enzymes Studies In Acute Renal
Failure Population Of Chennai
Abstract
The urinary marker enzymes of acute renal failure such as Acid Phosphatase, Alkaline Phosphatase, Lactate Dehydrogenase, Malate Dehydrogenase and Beta- Galactosidase were studied for their presence and their expression levels in acute renal failure patients and compared with that of the control groups. The level of marker enzymes were assayed using standard enzyme assays from the urine sample of acute renal failure subjects and were compared to the control groups. Substantial increase in Enzyme activity was noted in test subjects. Thus this study forms the basis for pre-diagnostic analysis to screen and detect acute renal failure in its early stages.
Key Words: Acid Phosphatase, Alkaline Phosphatase, Lactate Dehydrogenase, Malate Dehydrogenase and Beta- Galactosidase and Acute Renal Failure.
Introduction
Renal failure is the condition in which the kidneys fail to function properly (Levinsky, 1988). Physiologically, renal failure is described as a decrease in the glomerular filtration rate. Clinically, this manifest in an elevated creatinine level. The creatinine level is the most widely used biochemical test to assess renal function. Sophisticated methods do exist, but they are considered more costly and may not be widely applicable. Creatinine levels depend not only on kidney function, but on the person's existing muscle mass as well (Feest, 1993). Muscle mass varies with age, sex and race (Wardle, 1994). In this disease state, known in the medical field as cirrhosis, the creatinine level may look normal, but given the state of low muscle mass, may still be abnormal, and thus reflective of abnormal kidney function (Anderson and Schrier, 1997).
Causes of Kidney disease include Diabetic Nephropathy, Hypertension, Glomerulonephritis, Polycystic Kidney Disease, Reflux Nephropathy and Medications (Finn, 1993). Renal failure can be broadly classified into two categories: Acute Renal Failure and Chronic Renal Failure. The type of renal failure (acute vs. chronic) is determined by the trend in the serum creatinine. Other factors which may help to differentiate acute and chronic renal failure include the presence of anemia and the kidney size on ultrasound. Long-standing, i.e. chronic renal failure generally leads to anemia and small kidney size (Paller, 1994). Causes of acute kidney failure are generally categorized in relation to where and how they affect the kidneys, Prerenal if problems interfere with the flow of blood on its way to the kidneys, Renal if they are the cause that results in direct damage to the kidneys and Post renal comprising of problems with the flow of urine after it leaves the kidneys on its way out of the body (Conger, 1995).
Author: Indhumathi.
Topical Interest Review
Dysferlin:A Novel Defense Muscle Protein
Abstract
Dysferlin is a transmembrane protein present in the skeletal and cardiac muscle cell membranes. Dysferlin is coded by the gene DYSF in human chromosome 2p13.3-13.1. Dysferlin have several functions but it mainly acts as a calcium regulated fusogen in membrane repair mechanism. Mutation in DYSF gene results in two types of Muscular dystrophy (Limb-girdle and Miyoshi myopathy).Dysferlin deficiency in Muscular dystrophy patients leads to early onset of Cardiopmyopathy. There is no complete cure for Muscular dystrophy yet now. Thus using bioinformatics, the tertiary structure of dysferlin can be modeled. Mutant structure can also be predicted which acts as a target protein for lead compound identification.
Introduction
Specialized proteins in muscle cells are the building blocks of the structures constituting the moving machinery of muscle. There are three kinds of muscle viz., skeletal muscle, smooth muscle and cardiac muscle.
• Skeletal muscle is attached to bones and allows the voluntary movement of limbs;
• Smooth muscle is found in internal organs and aids in the involuntary movements that occur in the circulatory, digestive, excretory, reproductive, and respiratory systems;
• Cardiac muscle forms the powerful walls of the heart.
Muscle proteins indeed are essential for muscle functioning.Numerous muscle proteins are present in the sarcolemma membrane and they play their unique role for normal functioning of the muscle.Www.abc.net.au/ra/innovations/stories/s1729809.htm
Authors: P.Nandini bala,D.Kavitha.
Feature Critique
Bio Business: An Emerging Field of Biotechnology
Bio business in recent year has created unprecedented opportunities, not only for the manipulation of the biological system for the benefit of humankind; but also understanding fundamental process of life and global development. Bio business has become the world fastest growing and most rapidly changing field of biotechnology. A new concept in bio business comes into play calls recombinant DNA technology. Today a number of institutes public and private are working in the area of biotechnology with strong scientific system and product development in India. For example, Ranbaxy has successfully concluded 1.5 acquisitions since 2004, including 8 in 2006.
The company has expending international portfolio of affiliates, joint venture and representative office globally with presence in 23 of top 25 pharma markets. Ranbaxy invests $ 100 million for R&D sector. The story of Ranbaxy Company is that of very old keeping pace with times. Today it is the only Asian MNC to be counted in the top 10 generics player globally. The company was first Indian company to have an ambition to be come global company.
The Indian biotech industry is growing at a healthy phase. There is no doubt about this. To support this growing industry many related sectors have emerged in recent years. Biotech education is one such sector, which has expended its size and shape phenomenally in last five years.
Also a leading biotech company Biocon announced Biocon’s financial performance for the financial year ended March 31,2007. Biocon reported a total income of Rs 990 crore compared to the previous years business of 793 crore up by 25% consolidated revenues from the bio pharmaceutical and enzymes business grow 20 % to Rs 823 crore from Rs 680. It is entering the US market through a marketing company.
Authors:Sudhir Sharma,Deepa Garg.
Mini Review
RNAi –Silence even can speak further beyond…
Abstract
‘Silencing’- therapy is the most promising voice of the post-genomic era in developing new drugs and therapeutics for various diseases. This RNA-mediated genetic interference follows the revolutionary reverse genetic approach with a quest to decipher the functions and interactions of thousands of genes along with the development of genetic drugs. Here we give a briefing on the history and mechanism of RNAi induced silencing with special focus and forecast on some of the potential applications of gene suppression and a highlight of RNAi based-company profiles.
Key words: RNAi, Gene silencing, siRNA, apoptosis, miRNA.
Is it possible to measure Silence?? The most obvious answer will be no- just as you can’t measure darkness. So you can highly imagine the depth of the unmeasured “silence”. And when it is applied to an important issue of life- named as “gene” it becomes more meaningful. Gene Silencing – is the golden word in recent times. When the expression of a gene is silenced the result becomes more meaningful- meaningful to life and meaningful towards preventing death as well.
The password of such silencing is implanted into what is called RNA interference (RNAi). It has in it a therapeutic challenge to combat diseases starting right away from viral diseases to the deadly disease- cancer. These long double-stranded RNAs (dsRNAs; typically >200 nt) has brought about a new twist in the field of medical as well RNA-biology. They have the promising ability to knock down the expression of target genes in a variety of organisms and cell types (e.g., Worms, fruit flies, and plants) which is going to revolutionize reverse genetic approaches.Authors :Bibekanand Mallick, Zhumur Ghosh.